The present invention relates to a method for analyzing test results of bacteria susceptibility to antibiotics in order to assist doctors in prescribing a treatment. The analysis can more generally extend to tests of antimicrobial agents on micro-organisms.
A conventional analysis method consists in performing identification and antibiogram tests on a bacterial strain present in a sample, for example the blood of a patient. The identification aims at knowing more or less precisely the bacterial species to which the studied strain belongs. It is in particular performed by a macroscopic and microscopic observation, and carrying out tests by means of specific biochemical reagents. In general, the sole knowledge of the bacterial species is not sufficient to predict the efficiency of a given antibiotic on the studied strain. Indeed, for each family of antibiotics, the strains of a same species can have different resistance mechanisms, which will not always deactivate the same antibiotics within the family. The antibiogram consists in bringing together the studied bacterial strain and different antibiotics likely to be efficient on this strain. It is based on a more or less accurate measurement of the Minimum Inhibitory Concentration (MIC) of each of the antibiotics for the studied strain, that is, the minimum antibiotic concentration for which the strain ceases development.
Expert committees establish a first MIC threshold under which the tested species is designated xe2x80x9csusceptiblexe2x80x9d, and a second threshold above which the species is designated xe2x80x9cresistantxe2x80x9d. Between the two thresholds, the species is designated xe2x80x9cintermediatexe2x80x9d. This is the information generally provided to doctors.
Before being used by doctors as a basis to prescribe an antibiotic treatment, the result of the antibiogram is often interpreted. The aim of this interpretation is to detect possible test errors, or risks of inconsistency between the behavior of the studied strain confronted to a given antibiotic in vitro during the test and in vivo in the patient""s organism during the treatment. This approach is most often based on semi-empirical rules. For example, it enables detecting as erroneous a result xe2x80x9csusceptible to an antibioticxe2x80x9d when the studied strain belongs to a species systematically resistant to this antibiotic, or resistant to a related antibiotic known as systematically more active. In some cases, it is based on the knowledge of the possible resistance mechanisms for the species to which the studied strain belongs.
It is thus possible to correct or comment the results given for some antibiotics, when some elements hint that the strain has a resistance mechanism which may express less in vitro than in the organism. This interpretation also involves notions in appreciating the risk for the patient: in case of doubt for an antibiotic, it is generally preferred to state that a strain is resistant, if there are other antibiotics available for a treatment, to which the strain has been found to be susceptible with unambiguously.
Present analysis systems perform the test in an automated way and are able to indicate, for each tested antibiotic, whether the species is resistant, intermediate or susceptible. Further, some of these systems enable an automation of part of the interpretation, especially by using a rule database. The rule databases implemented in these systems most often reproduce the semi-empirical rules conventionally used. Now, these rules are efficient only to detect and correct some predetermined error cases. A problem thus is the implementation of an interpretation method enabling detection of all error types and the provision, if possible, of their correction.
The recognition of the resistance mechanisms which may poorly express in vitro is required to correct or comment the results. The rule databases implemented in present systems are based on the classification as xe2x80x9csusceptiblexe2x80x9d, xe2x80x9cintermediatexe2x80x9d, or xe2x80x9cresistantxe2x80x9d, and closely depend on the list of tested antibiotics. In a great number of cases, they do not enable accurate detection of the resistance mechanism.
Further, the pairs of MIC thresholds determining the xe2x80x9csusceptiblexe2x80x9d, xe2x80x9cintermediatexe2x80x9d, and xe2x80x9cresistantxe2x80x9d categories, being fixed by national expert committees, are likely to be modified in time and differ from one country to another, or even sometimes from one laboratory to another in some countries. The same occurs for recommendations concerning the required behavior in case a resistance mechanism that may poorly express in vitro shows up. Thus, different rule bases corresponding to the interpretative choices of the different national expert committees and enabling adaptation of the rules according to the laboratories have to be provided. Such rule bases are particularly complex and their development amounts to considerable work.
An object of the present invention is to provide an analysis method for susceptibility tests which is independent of the interpretative choices of expert committees, which enables detecting and correcting errors without having to forsee the error cases to process, and which provides, in most cases, an accurate indication of the resistance mechanisms of a tested strain for the different antibiotic families.
These objects are achieved by means of a method for analyzing test results of micro-organism susceptibility to antimicrobial agents, the test consisting of roughly identifying the species to which a micro-organism belongs and of measuring the minimum inhibitory concentrations (MIC) of several antimicrobial agents for this micro-organism. The method uses a database indexing the micro-organism species as well as their resistance mechanisms against different antimicrobial agents, and containing, for each species and each resistance mechanism, parameters characteristic of statistic MIC distributions for a group of antimicrobial agents.
According to an embodiment of the invention, the method includes the steps of extracting from the database the parameters of the distributions associated with the resistance mechanisms of the identified species and with the antimicrobial agents used to perform the test; comparing the MICs measured during the test with the extracted parameters; and indicating that the test is valid when the measured MICs correspond to the extracted parameters associated with at least one predetermined resistance mechanism of the identified species.
According to an embodiment of the invention, the method includes the step of indicating the predetermined resistance mechanism.
According to an embodiment of the invention, the method includes, when the test is not valid, a step of determining corrections to be performed on at least one of the measured MICs, the choice of the corrections fulfilling predetermined optimality criteria.
According to an embodiment of the invention, the method includes, when the test is not valid, the steps of extracting from the database the parameters of the MIC distributions associated with the resistance mechanisms of other species and with the antimicrobial agents used for the testing; comparing the measured MICs with the extracted parameters; and determining the species for which at least one resistance mechanism, per tested antimicrobial agent family, is identifiable based on the measured MICs.
According to an embodiment of the invention, the database contains information indicating, for species with a given resistance mechanism and for given antimicrobial agents, an in vivo resistance which may be higher than the in vitro resistance.
According to an embodiment of the invention, the distribution parameters stored in the database include the classes of MIC values and the normalized absolute frequencies, the method including, for an untested antimicrobial agent, the steps of extracting from the database the classes and absolute frequencies associated with the predetermined resistance mechanism and the untested antimicrobial agent; keeping the classes for which the absolute frequencies exceed a predetermined threshold; confronting the kept classes with two normalized MIC thresholds defining xe2x80x9csusceptiblexe2x80x9d, xe2x80x9cintermediatexe2x80x9d, and xe2x80x9cresistantxe2x80x9d categories of a micro-organism; and indicating the categories located on either side of each of the normalized thresholds located in the retained classes.
The foregoing and other objects, features and advantages of the present invention will be discussed in detail in the following non-limiting description of specific embodiments in connection with the accompanying drawings.